title: Deficiency of complement component 5 ameliorates glaucoma in DBA/2J mice.
abstract: BACKGROUND
  Glaucoma is an age-related neurodegenerative disorder involving the loss of retinal ganglion cells (RGCs), which results in blindness. Studies in animal models have shown that activation of inflammatory processes occurs early in the disease. In particular, the complement cascade is activated very early in DBA/2J mice, a widely used mouse model of glaucoma. A comprehensive analysis of the role of the complement cascade in DBA/2J glaucoma has not been possible because DBA/2J mice are naturally deficient in complement component 5 (C5, also known as hemolytic complement, Hc), a key mediator of the downstream processes of the complement cascade, including the formation of the membrane attack complex.
  
  
  METHODS
  To assess the role of C5 in DBA/2J glaucoma, we backcrossed a functional C5 gene from strain C57BL/6J to strain DBA/2J for at least 10 generations. The prevalence and severity of glaucoma was evaluated using ocular examinations, IOP measurements, and assessments of optic nerve damage and RGC degeneration. To understand how C5 affects glaucoma, C5 expression was assessed in the retinas and optic nerves of C5-sufficient DBA/2J mice, using immunofluorescence.
  
  
  RESULTS
  C5-sufficient DBA/2J mice developed a more severe glaucoma at an earlier age than standard DBA/2J mice, which are therefore protected by C5 deficiency. Components of the membrane attack complex were found to be deposited at sites of axonal injury in the optic nerve head and associated with RGC soma in the retina.
  
  
  CONCLUSIONS
  C5 plays an important role in glaucoma, with its deficiency lessening disease severity. These results highlight the importance of fully understanding the role of the complement cascade in neurodegenerative diseases. Inhibiting C5 may be beneficial as a therapy for human glaucoma.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, USA. gareth.howell@jax.org
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Howell
authors.forename: Ileana
authors.initials: I
authors.lastname: Soto
authors.forename: Margaret
authors.initials: M
authors.lastname: Ryan
authors.forename: Leah C
authors.initials: LC
authors.lastname: Graham
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
mesh_terms: D000818:Animals; D003182:Complement C5 / Q000172:deficiency*; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012720:Severity of Illness Index
chemical_list: D003182:Complement C5